OBJECTIVE To investigate the efficacy and safety of atezolizumab plus donafenib in patients with advanced unresectable hepatocellular carcinoma （uHCC）.METHODS Patients with uHCC treated at the Dept. of Hepatobiliary and Pancreatic Surgery， The First Hospital of Hebei Medical University， from May 1， 2023 to April 30， 2025 were selected as study subjects for a retrospective study. All patients received interventional therapy with transcatheter arterial chemoembolization （TACE） and/or hepatic arterial infusion chemotherapy （HAIC）. On this basis， patients were divided according to the systemic treatment regimen into a control group （atezolizumab plus bevacizumab， n ＝56） and an observation group （atezolizumab plus donafenib， n ＝49）. Short-term efficacy at 3 months after treatment and long-term efficacy were compared between the two groups. Subgroup analyses were further performed with sex， age， hepatitis B， liver cirrhosis， Child-Pugh class， Barcelona Clinic Liver Cancer （BCLC） stage， Eastern Cooperative Oncology Group Performance Status （ECOG-PS） score， tumor number， maximum tumor diameter， portal vein tumor thrombus， and interventional treatment modality as subgroup variables， with interaction tests conducted between subgroup variables and treatment group. Adverse reactions during treatment were compared between the two groups.RESULTS At 3 months after treatment， the disease control rate was significantly higher in the observation group than in the control group （ P ＜0.05）， whereas the difference in objective response rate between the two groups was not statistically significant （ P ＞0.05）. The median progression-free survival was 7.53 months [95% confidence interval （CI）： 6.32-8.53 months] in the control group and 8.06 months （95%CI： 7.33-9.70 months） in the observation group， with no statistically significant difference between the two groups （ P ＞0.05）. The median overall survival was 13.56 months （95%CI： 11.23-15.77 months） in the control group and 14.92 months （95%CI： 12.93-17.11 months） in the observation group， and overall survival was significantly longer in the observation group than in the control group （ P ＜0.05）. Subgroup analysis showed that among patients with Child-Pugh class A， BCLC stage B， or without portal vein tumor thrombus， the risk of death was lower in the observation group than in the control group， with hazard ratios of 0.46， 0.49 and 0.44， respectively， and interaction P values of 0.035， 0.008 and 0.013， respectively. Adverse reactions in both groups were mainly grade 1-2， and there were no statistically significant differences in the incidence of individual adverse reactions between the two groups （ P ＞0.05）.CONCLUSIONS In patients with advanced uHCC receiving interventional therapy， the atezolizumab plus donafenib regimen was associated with a higher disease control rate and longer overall survival， and this association was mainly observed in patients with Child-Pugh class A， BCLC stage B， or without portal vein tumor thrombus.

Objective To investigate the therapeutic effect of Ziwuliuzhu acupuncture in a rat model of insomnia and its regulatory effect on the glutamic acid(Glu)/γ-aminobutyric acid(GABA)-glutamine(Gln)metabolic loop.Methods Forty male SD rats were randomly assigned to control group,model group,Najia group and Nazi group(n=10).In the latter 3 groups,rat models of insomnia were established by intraperitoneal injections of p-chlorophenylalanine and verified using a sodium pentobarbital-induced sleep test.After modeling,the rats in Najia and Nazi groups received acupuncture for 7 days at specifically chosen sets of acupoints based on the Ziwuliuzhu rationale in traditional Chinese medicine.Pathological changes in the hypothalamic tissue of the rats were examined with HE staining,and the levels of Glu and GABA in the hypothalamus were determined with high-performance liquid chromatography(HPLC)-mass spectrometry(MS)/MS.Immunohistochemistry was used to detect the expressions of GABAA receptors(GABAARs)in the hypothalamus,and the expression levels of glutamate decarboxylase(GAD65/67)and glutamine synthetase(GS)were determined with Western blotting.Results Compared with the model group,the rats in Najia and Nazi groups exhibited decreased Glu levels and GABAA receptor expression and increased GABA levels with a decreased Glu/GABA ratio in the hypothalamus.Ziwuliuzhu acupuncture significantly increased the protein expressions of GAD65 and GAD67 and lowered the expression of GS in the hypothalamus in the rat models of insomnia.Conclusion Ziwuliuzhu acupuncture produces sedative and hypnotic effects in rat models of insomnia possibly by regulating Glu and GABA-Gln metabolism to restore the excitatory/inhibitory balance between Glu and GABA.

OBJECTIVES: To investigate the therapeutic effect of Ziwuliuzhu acupuncture in a rat model of insomnia and its regulatory effect on the glutamic acid (Glu)/γ-aminobutyric acid (GABA)-glutamine (Gln) metabolic loop. METHODS: Forty male SD rats were randomly assigned to control group, model group, Najia group and Nazi group (n=10). In the latter 3 groups, rat models of insomnia were established by intraperitoneal injections of p-chlorophenylalanine and verified using a sodium pentobarbital-induced sleep test. After modeling, the rats in Najia and Nazi groups received acupuncture for 7 days at specifically chosen sets of acupoints based on the Ziwuliuzhu rationale in traditional Chinese medicine. Pathological changes in the hypothalamic tissue of the rats were examined with HE staining, and the levels of Glu and GABA in the hypothalamus were determined with high-performance liquid chromatography (HPLC)-mass spectrometry (MS)/MS. Immunohistochemistry was used to detect the expressions of GABAA receptors (GABAARs) in the hypothalamus, and the expression levels of glutamate decarboxylase (GAD65/67) and glutamine synthetase (GS) were determined with Western blotting. RESULTS: Compared with the model group, the rats in Najia and Nazi groups exhibited decreased Glu levels and GABAA receptor expression and increased GABA levels with a decreased Glu/GABA ratio in the hypothalamus. Ziwuliuzhu acupuncture significantly increased the protein expressions of GAD65 and GAD67 and lowered the expression of GS in the hypothalamus in the rat models of insomnia. CONCLUSIONS Ziwuliuzhu acupuncture produces sedative and hypnotic effects in rat models of insomnia possibly by regulating Glu and GABA-Gln metabolism to restore the excitatory/inhibitory balance between Glu and GABA.
Animals ; Rats, Sprague-Dawley ; Male ; Rats ; gamma-Aminobutyric Acid/metabolism* ; Sleep Initiation and Maintenance Disorders/therapy* ; Glutamine/metabolism* ; Glutamic Acid/metabolism* ; Acupuncture Therapy ; Hypothalamus/metabolism* ; Receptors, GABA-A/metabolism* ; Acupuncture Points

Objective:The impact and mechanism system of the National Centralized Volume-Based Procurement(NCVBP)on innovation investment in pharmaceutical companies.Methods:Based on listed company data from 2015 to 2023,it uses the first eight rounds of NCVBP as a quasi-natural experiment and applies a staggered difference-in-differences model to control the industries and year fixed effects,test the impact of NCVBP on innovation investment in pharmaceutical companies,conduct the parallel trend and placebo test,and verify the robustness of the results.Results:The innovation investment of the winning enterprises was significantly increased by NCVBP.The ratio of Research&Development expenses to operating revenues of winning firms in the next quarter increases by 1.4%.The centralized procurement promotes innovation investment by enhancing the cost efficiency of enterprises and strengthening market competition in the industry.Conclusion:Collective purchasing significantly increases the innovation investment of winning enterprises,the improvement of cost efficiency is an important influence path to improve the innovation investment of enterprises.The industry market competition has a significant moderating effect on the collective purchasing and the innovation investment of enterprises;the national drug collective purchasing system can be improved from the aspects of innovation incentives,communication system,market competition,and so on.

Metabolic associated fatty liver disease(MAFLD)is a metabolic disorder liver disease closely related to insulin resistance(IR)and genetic susceptibility.Hepatocyte steatosis is the main pathological change.In recent years,the prevalence of MAFLD has increased significantly,so it is necessary to provide interventions as soon as possible.Glucagon-like peptide-1 receptor agonist plays a hypoglycemic effect by promoting insulin release and reducing IR.Studies shows that it has significant benefits on body weight,lipid metabolism,inflammation and fibrosis in patients with MAFLD,and is expected to be an effective drug for the treatment of MAFLD.

Sarcopenia refers to the gradual decrease in skeletal muscle mass and function with age,and is an important factor in disability and mortality in elderly population.The pathogenesis of sarcopenia may be related to insulin resistance,oxidative stress,inflammation,mitochondrial dysfunction,and impaired autophagy caused by abnormal glucose and lipid metabolism.Sarcopenia can reduce daily activity ability and prolong recovery time from diseases.This article reviews the research progress on the relationship between abnormal glucose and lipid metabolism and the pathogenesis of sarcopenia.

Objective:The impact and mechanism system of the National Centralized Volume-Based Procurement(NCVBP)on innovation investment in pharmaceutical companies.Methods:Based on listed company data from 2015 to 2023,it uses the first eight rounds of NCVBP as a quasi-natural experiment and applies a staggered difference-in-differences model to control the industries and year fixed effects,test the impact of NCVBP on innovation investment in pharmaceutical companies,conduct the parallel trend and placebo test,and verify the robustness of the results.Results:The innovation investment of the winning enterprises was significantly increased by NCVBP.The ratio of Research&Development expenses to operating revenues of winning firms in the next quarter increases by 1.4%.The centralized procurement promotes innovation investment by enhancing the cost efficiency of enterprises and strengthening market competition in the industry.Conclusion:Collective purchasing significantly increases the innovation investment of winning enterprises,the improvement of cost efficiency is an important influence path to improve the innovation investment of enterprises.The industry market competition has a significant moderating effect on the collective purchasing and the innovation investment of enterprises;the national drug collective purchasing system can be improved from the aspects of innovation incentives,communication system,market competition,and so on.

Sarcopenia refers to the gradual decrease in skeletal muscle mass and function with age,and is an important factor in disability and mortality in elderly population.The pathogenesis of sarcopenia may be related to insulin resistance,oxidative stress,inflammation,mitochondrial dysfunction,and impaired autophagy caused by abnormal glucose and lipid metabolism.Sarcopenia can reduce daily activity ability and prolong recovery time from diseases.This article reviews the research progress on the relationship between abnormal glucose and lipid metabolism and the pathogenesis of sarcopenia.

Metabolic associated fatty liver disease(MAFLD)is a metabolic disorder liver disease closely related to insulin resistance(IR)and genetic susceptibility.Hepatocyte steatosis is the main pathological change.In recent years,the prevalence of MAFLD has increased significantly,so it is necessary to provide interventions as soon as possible.Glucagon-like peptide-1 receptor agonist plays a hypoglycemic effect by promoting insulin release and reducing IR.Studies shows that it has significant benefits on body weight,lipid metabolism,inflammation and fibrosis in patients with MAFLD,and is expected to be an effective drug for the treatment of MAFLD.

Percutaneous nephrolithotomy(PCNL)is the first-line treatment for complex kidney stones and can be performed in a variety of positions.Semi-supine combined lithotomy position,as a flexible,convenient,safe and effective position for PCNL,can be conducted in a retrograde approach under a single position,so it is suitable for the treatment of complex kidney stones.We will review the development characteristics and advantages of PCNL in semi-supine combined lithotomy position,and its application in the treatment of complex kidney stones.Based on this,we will further propose a minimally invasive treatment strategy for upper urinary tract calculi.